title: Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials.
abstract: OBJECTIVE
  In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen?
  
  
  METHODS
  TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization.
  
  
  RESULTS
  TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and late-2014.
  
  
  CONCLUSIONS
  We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer. Trial Registration TEXT: Clinicaltrials.govNCT00066703 SOFT: Clinicaltrials.govNCT00066690.
authors.affiliation: International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: mregan@jimmy.harvard.edu.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Walley
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Manuela
authors.initials: M
authors.lastname: Rabaglio
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruepp
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Francis
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000528:radiation effects / Q000601:surgery; D017697:Premenopause; D012107:Research Design; D013223:Statistics as Topic; D013629:Tamoxifen / Q000627:therapeutic use*; D017329:Triptorelin Pamoate / Q000494:pharmacology
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D017329:Triptorelin Pamoate; D013629:Tamoxifen; C056516:exemestane
keywords: Adjuvant therapy; Early breast cancer; Endocrine-responsive; Premenopausal; Trial design